Studies of Contact Hypersensitivity Induction in Mice with Optimal Sensitizing Doses of Hapten

To avoid unsuspected and unwanted consequences of excess hapten during epicutaneous sensitization, optimal sensitizing doses of dinitrofluorobenzene (DNFB) were determined for several ultraviolet B radiation (UVB)–resistant and UVB- susceptible strains of mice. Using these doses of hapten applied epicutaneously or injected intracutaneously into normal or UVB-exposed body wall skin, it was determined that four consecutive daily exposures to UVB prevented contact hypersensitivity induction in all mice when optimal sensitizing doses of DNFB were applied epicutaneously. By contrast, UVB-resistant, but not UVB-susceptible, mice developed contact hypersensitivity when an optimal sensitizing dose of DNFB was injected intracutaneously into UVB-irradiated skin. Moreover, whereas UVB-susceptible mice failed to develop contact hypersensitivity when an optimal sensitizing dose of DNFB was painted on skin exposed to a single dose of UVB, UVB-resistant mice did develop contact hypersensitivity under similar circumstances. Based on these results, it is concluded that 1) conventional doses of epicutaneously applied haptens induce contact hypersensitivity with the aid of antigen-presenting cells derived from both the epidermis and the dermis, 2) the phenomenon of UVB susceptibility is mediated by cells and molecules within the dermis when conventional doses of hapten and UVB radiation are employed, and 3) UVB susceptibility is mediated by cells and molecules within the epidermis when optimal sensitizing doses of hapten and a single exposure to UVB are employed

A Substance p Agonist Acts as an Adjuvant to Promote Hapten-Specific Skin Immunity

Because substance p (SP) has been reported to be released from cutaneous sensory nerve endings after hapten application, we determined whether SP participates in contact hypersensitivity (CH) induction by using a SP agonist, GR73632 or δ-Aminovaleryl [Pro9, N-Me-Leu10[-substance P7–11 and a SP antagonist, spantide I. When injected intradermally, SP agonist enhanced CH induced by conventional, but not optimal, sensitizing doses of hapten. By contrast, SP antagonist inhibited the induction of CH by optimal sensitizing doses of hapten. Moreover, SP agonist promoted CH induction and prevented tolerance when hapten was painted on skin exposed to acute, low-dose ultraviolet-B radiation. Intradermally injected SP agonist altered neither the density nor the morphology of epidermal Langerhans cells, implying that SP agonist enhanced the generation of hapten-specific immunogenic signals from the dermis. It is proposed that SP is a natural “adjuvant” that promotes the induction of CH within normal skin. Although exogenous SP agonist can prevent impaired CH and tolerance after ultraviolet-B radiation, the susceptibility of native SP to local neuropeptidases renders the neuropeptide unable to prevent the deleterious effects of ultraviolet-B radiation on cutaneous immunity

Choroidal Metastasis of Non-Small Cell Lung Cancer That Responded to Gefitinib

A 52-year-old Japanese woman presented with optical symptoms, including left-sided myodesopsia, blurred vision, narrowed visual field, and diminished visual acuity. Ocular evaluation revealed a metastatic tumor in the choroid. Further examinations identified pulmonary adenocarcinoma as the primary tumor. Because an epidermal growth factor receptor gene (EGFR) mutation was detected in a biopsy specimen, gefitinib treatment was initiated. Dramatic responses were obtained in the primary tumor and metastatic foci. Optical symptoms improved and remained stable for 5 months during the treatment, until relapse. This report demonstrates that gefitinib is effective for choroidal metastasis of pulmonary adenocarcinoma harboring an EGFR mutation